PubMed · 4885602
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P G Schilew, W P Babmindra. 1968. [Experimental morphological studies on interneuronal synapses].. https://pubmed.ncbi.nlm.nih.gov/4885602/
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The lysozyme gene is expressed at a low level in myeloblasts and is progressively activated to constitutively high expression in mature macrophages. The binding activity of the newly defined NF-kappa B/Rel family of transcription factors increases during the terminal differentiation of macrophages. In this study, I show that NF-kappa B/Rel-like proteins bind to the nuclear factor kappa B (kappa B)-like sequence of the lysozyme promoter. These binding activities were induced by treatment of HD11 cells with lipopolysaccharide. Immunomobility shift assays show that c-Rel is possibly a factor in the complexes that bind to the kappa B-like sequence lys kappa B. Binding activity to one of the protein complexes seems to be regulated by phosphorylation. In fact, overexpression of p65 and c-Rel stimulates expression of the chloramphenicol acetyltransferase gene controlled by the lysozyme promoter. Furthermore, co-transfection experiments reveal that the kappa B-like sequence within the lysozyme promoter mediates the transactivation by p65 and c-Rel. These results indicate that the p65 and c-Rel could be components of the protein complexes that bind to the kappa B-like sequence and this binding could contribute to the progressively activated expression of the lysozyme gene during the terminal differentiation of macrophages.
OBJECTIVES: The safety, efficacy, and pharmacokinetics of the nonsteroidal antiandrogen bicalutamide were investigated in a Phase II trial in 150 patients with metastatic prostate cancer. METHODS: Patients took bicalutamide, 50 mg daily, in an open-label multicenter North American trial. RESULTS: The objective response rate (modified European Organization on Research and Treatment of Cancer [EORTC] criteria) was 70% (57% partial, 13% stable); 59 (39%) of 150 patients had either a > 90% decrease in prostate-specific antigen (PSA) levels or a decline to < 4 ng/mL. Extent of disease on the bone scan was a significant predictor of response. Patients with < 6 metastatic lesions were more likely to respond. Breast pain and gynecomastia occurred in 76% and 60% of patients, respectively. Gastrointestinal toxicity was very infrequent (diarrhea, 5%) The mean drug plasma concentration was 8528 (+/- 2928) ng/mL. CONCLUSIONS: Bicalutamide, 50 mg daily, was well tolerated and has efficacy in metastatic prostate cancer. The percentage of men who had > 90% decline in PSA levels is less than observed with surgical or medical castration and has led to trials using this antiandrogen at higher doses as monotherapy.